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Biomedical subjects

M Salzer-Kuntschik

Publications and source records attributed to M Salzer-Kuntschik.

At least 19 recordsLinked to original sources
PubMed1995

High nm23-H1/NDPK-A expression in Ewing tumors: paradoxical immunohistochemical reactivity and lack of prognostic significance.

Expression of nm23-H1/NDPK-A has been reported to correlate inversely with metastasizing potential of rodent experimental cells and some human tumors. In the search for reliable molecular prognostic indicators for Ewing tumors (ET), a group of aggressive presumably neuroectodermal malignancies in children and adolescents, we studied nm23-H1/NDPK-A expression. Northern-blot and RT-PCR analyses were employed to semi-quantificatively measure nm23-H1 mRNA levels in ET cell lines and tissue extracts. A panel of monoclonal antibodies (MAbs) were used to evaluate protein abundance by Western blotting and immunohistochemistry. The nm23-H1/NDPK-A gene was also investigated on the DNA level to define possible genomic alterations. Our results revealed neither nm23-H1 allelic loss nor gene amplification and failed to show any significant variation in nm23-H1 mRNA or NDPK-A protein levels of primary or metastatic ET. NDPK-A protein levels were high and comparable to those of MCF-7 breast-cancer cells and to aggressive stage-IV neuroblastoma cell lines. nm23-H2/NDPK-B expression in ET was slightly more variable but generally lower than in MCF-7 cells. In the immunohistochemical analysis, however, discrepancies in the reactivity patterns with different antibodies were observed. Differential sensitivity to various fixation methods and heat treatment pointed to a structurally polymorphic NDPK-A protein. nm23-H1 expression studies using immunohistochemistry for prognostic counselling should thus be interpreted with caution.

Adolescent↗
PubMed1994

Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data.

Ewing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric transcripts can be readily detected by reversed transcriptase polymerase chain reaction (RT-PCR). This approach led to the identification of a number of different exon combinations at the junction site of coding sequences. The physiological consequences of the observed variability in the hinge region of EWS chimaeric proteins are not known. We have analysed tumour-derived material from 30 ET patients with well-documented clinical course (18 with localised and 12 with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%). In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7 (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in one case each. In the last tumour, the presence of at least four additional splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8 and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations 7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and were more abundant in tumours affecting the long bones (9 versus 0), whereas in central axis tumours and metastatic disease there was only little difference in the frequency of the two types. So far, no correlations between different chimaeric EWS transcripts and any other clinical parameters have been identified.

Adolescent↗
PubMed1992

Morphometric analysis of cartilaginous tumors.

144 chondromas and chondrosarcomas have been investigated. Morphometry has been performed: the relative volume density of tumor cell nuclei (Vv%n) and the nuclear area have been measured. The results show that the relative volume density of nuclei is a useful parameter, regarding the localisation of the tumors, to discriminate chondromas and chondrosarcomas, while the nuclear area is no safe criterion to separate these entities.

Cell Nucleus↗
PubMed1991

Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86.

The Cooperative Ewing's Sarcoma Studies, CESS 81 and CESS 86, are multiinstitutional trials with more than 80 participating institutions from Germany, the Netherlands, Austria, and Switzerland. Treatment consists of four courses of multiagent chemotherapy and local therapy. Local therapy was not randomized and was either radical surgery or resection plus postoperative irradiation or definitive radiation therapy. Here results according to local therapy have been analyzed for 93 protocol patients with localized Ewing's sarcoma (ES) who have been recruited in CESS 81 from January 1981 to February 1985 and 122 protocol patients recruited in CESS 86 from January 1986 to November 1989. The 3-year relapse-free survival (RFS) was 55% in CESS 81 and 62% in CESS 86. In CESS 81, the RFS was better for surgically treated than for irradiated patients. In this study there was an extremely high incidence of local failures (50%) after definitive irradiation. In CESS 86, however, the results after radiation therapy have been improved markedly (3-year RFS 67% after radiation therapy, 65% after surgery, and 62% after resection plus irradiation). Possible explanations for the improvement of radiotherapeutic results are as follows: selections for patients for radiation therapy, start of local therapy, and quality of radiation therapy. In CESS 86, irradiated patients were randomized to receive either conventionally fractionated irradiation with less intense chemotherapy or hyperfractionated irradiation with simultaneous chemotherapy. There was no difference in treatment results at the time of analysis. The authors conclude that selection of patients for local treatment modalities and quality of treatment performance has an impact on local and overall treatment results in ES.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration.

This study reports on the specific expression of the MIC2 gene, a pseudoautosomal gene located on the short arms of the X and Y chromosomes, on Ewing's sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cells. The gene product, a cell membrane protein, is recognized by the newly established monoclonal antibody (MoAb) HBA-71 and the previously described MoAb 12E7 and RFB-1. Furthermore, the reaction pattern of the MIC2 antibodies, especially HBA-71, with normal tissues and a great number of benign and malignant tumors (70 different tumors, 199 tumor samples), as well as the correlation between the specific chromosomal aberrations, i.e., the t(11;22) and the del(22) and the expression of this antigen, are demonstrated. Both ES and pPNET cells express the MIC2 gene in very high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely. The MIC2 antibodies are of great value for clinical and research purposes.

12E7 Antigen↗
PubMed1991

Devitalizing effects of phenol on bone marrow cells. Histologic study on cadaveric animal vertebrae.

The devitalizing effects of 5-90 percent phenol for 30 seconds on bone marrow cells were examined on vertebral bodies of fresh animal cadavers. Evaluation was made by measuring the width of the zone of necrotic cells. The zone increased with rising phenol concentration up to 75 percent, reaching an average width of 0.75 mm. However, when protected by bone trabeculae, the cells escaped devitalization.

Animals↗
PubMed1991

Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry.

The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable.

Adolescent↗
PubMed1991

The management of IIB osteosarcoma. Experience from 1976 to 1985.

From 1976 to 1985, 75 IIB osteosarcomas have been treated out of a total of 98 osteosarcomas at the authors' institution. Because of the effective chemotherapy including high-dose methotrexate administered during this time period, the surgical management changed, and only ten patients out of the 75 IIB osteosarcomas required an amputation. The overall result of 76.7% of disease-free, three-year survival was equally distributed regardless of the surgical procedure. Endoprosthesis, resection with or without grafts, and rotationplasties, as well as amputations, revealed similar results. No negative influence from the limb-sparing surgery could be observed.

Adolescent↗
PubMed1990

Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86).

In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.

Adolescent↗
PubMed1989

Immunohistochemical detection of the c-erbB-2 proto-oncogene product in normal, benign and malignant cartilage tissues.

Benign and malignant cartilage tumours as well as normal cartilage were stained immunohistochemically with antibodies raised to a synthetic peptide from the sequence of the c-erbB-2 protein. Positive staining was present in 18/23 of the chondrosarcomas and in one case of osteochondroma. Normal and benign neoplastic cartilage tissues revealed negative results. It is concluded that expression of the c-erbB-2 protein may contribute to cell transformation in chondrosarcomas; it is not apparent whether the expression of c-erbB-2 protein in chondrosarcomas characterizes a subpopulation of different prognostic significance.

Cartilage↗
PubMed1989

[Results of treatment in primary disseminated osteosarcoma. Analysis of the follow-up of patients in the cooperative osteosarcoma studies COSS-80 and COSS-82].

Since the long-term disease-free survival rate in adjuvantly treated osteosarcoma has nowadays reached a level of about 70%, increasing interest is also being directed towards primarily disseminated forms of the disease. Primary metastases, which were confined to the lungs in 42 cases, were detected in 59 out of 421 patients from the prospective therapy trials COSS-80 and COSS-82. The primary tumors were more frequently localized in the proximal femur and flat bones as compared to patients without detectable metastases at diagnosis. Following chemotherapy and surgery of the primary tumor, 15/31 (48%) patients whose metastases were excised have survived for 4-8 years, in contrast to only 1/22 (5%) of those patients whose metastases could not be removed for a variety of reasons. Clinical or histological evidence of tumor response after primary chemotherapy significantly influenced the outcome of the metastasectomized patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The angiographic response of osteosarcoma following pre-operative chemotherapy.

The prognosis of osteosarcoma has improved significantly with recent advances in chemotherapy. Evaluation of the effect of chemotherapy is important for optimal timing of surgery, for selecting an alternative drug regimen in instances of poor response to chemotherapy and for testing combinations of new drugs. The purpose of this paper is to define the value of plain radiographs and angiography in assessing tumor response to chemotherapy. Studies were obtained before and after chemotherapy. The radiographic results were correlated with histologic evaluation of the resected specimen. Patients with less than 10% residual viable tumor in the resected bone were designated "responders" and patients with more than 10% of remaining viable tumor were "nonresponders". Angiographic appearances correctly separated 15 patients with good response to chemotherapy from seven patients who were not responsive. Conversely, comparison of plain radiographs obtained before and after chemotherapy did not allow a reliable differentiation between patients with good, poor, or no response to chemotherapy. The current role of angiography in the management of patients with osteosarcoma is discussed. It is concluded that - in contrast to plain film radiography - angiography is an accurate method for assessing the response of osteosarcoma to chemotherapy.

Adolescent↗
PubMed1985

Nuclear polymorphism in osteosarcomas as a prognostic factor for the effect of chemotherapy. A quantitative study.

A current strategy for osteosarcoma treatment is neo-adjuvant chemotherapy prior to the resection of the tumour. It appears that some tumours respond very well to the cytostatic therapy, while others show little or no effect. It is desirable to be able predict the response of the tumour before starting chemotherapy. 16 biopsy specimens from patients with osteosarcoma who had been treated according to the protocol of the study COSS-80 and COSS-82 were examined. 100 tumour cells from each biopsy have been measured by an electronic interactive image analysis system (IBAS II; Kontron/ZEISS). After completion of chemotherapy en bloc resection of the tumour was performed. The entire surgical specimen was completely examined at two levels by means of undecalcified sections, and assigned a grade for the effect of chemotherapy analogous to the grading of Salzer-Kuntschik et al. (1983). The quantitative analysis of tumour cell nuclei revealed two different patterns of nuclear sizes, which were correlated significantly with the chemotherapy response (P less than 0.002). Tumour cell nuclei of well responders were significantly larger and showed a greater variance in size (mean value 66 + 41 micron 2), than those of poor responders (mean value 38 + 18 micron 2). We conclude from our results that quantitative analysis and classification of nuclear size of osteosarcoma cells may be useful for predicting chemotherapy response in patients with osteosarcoma.

Adolescent↗
PubMed1984

Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study.

From December 1979 to August 1982 158 patients were registered for an adjuvant chemotherapy (CT) study COSS -80. To compare the effect of cisplatin (CPL) to that of the drug combination bleomycin, cyclophosphamide, and dactinomycin (BCD), patients were randomized to receive either drug(s) within a course of sequential multidrug CT including doxorubicin and high-dose methotrexate (HDMTX). Definite surgery was done 10-18 weeks after the start of CT. Patients were randomized a second time to receive or not to receive fibroblast interferon in addition to CT beginning at week 16. At a median observation time of 19.5 months (range, 4-34 months), 116 (73%) of 158 patients were continuously disease-free (CDF). After exclusion of 42 patients because of some deviation in history and/or management, 86 (74%) of 116 patients actually were CDF with a 30-month calculated CDF-rate of 68%. There was no difference in CDF rates in the patients receiving BCD versus CPL or receiving interferon versus no interferon. Whereas, in comparison to the previous study COSS -77, the over-all increase in CDF rate does not reach statistical significance, it does, however, for the younger (less than or equal to 12 years) and for male patients, which is assumed to be the effect of increasing the methotrexate dose from 6 to 12 g/m2 in the COSS -80 study.

Adolescent↗
PubMed1983

Adjuvant chemotherapy in osteosarcoma - effects of cisplatinum, BCD, and fibroblast interferon in sequential combination with HD-MTX and adriamycin. Preliminary results of the COSS 80 study.

In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.

Adult↗
PubMed1983

Morphological grades of regression in osteosarcoma after polychemotherapy - study COSS 80.

The histologic grade of regression of 50 osteosarcomas after polychemotherapy - according to the protocol study, COSS 80 - was classified on a six-stage regression scale; 56% of all patients responded well to chemotherapy regression grades I, II, and III and no significant difference between BCD- and CPL-treated patients could be found. Tumors under 10 cm in length responded better to chemotherapy than those of greater length and there was a good correlation between the clinical estimation of tumor regression and progression and the histologic grade of regression.

Antineoplastic Agents↗